Redox Imbalance in ADHD: A Meta-Analysis of Oxidative Stress and Antioxidant Biomarkers (2010-2025)

Oxidative-antioxidant imbalance has been proposed as a biological contributor to attention-deficit/hyperactivity disorder (ADHD), yet findings across biomarkers, age groups and assay platforms remain heterogeneous. We synthesised evidence on oxidative damage markers (malondialdehyde [MDA], 8-hydroxy-2'-deoxyguanosine [8-OHdG]), global redox indices (total oxidant status [TOS], oxidative stress index [OSI], total antioxidant status [TAS]) and enzymatic antioxidants (superoxide dismutase [SOD], glutathione peroxidase [GPx], catalase [CAT]).

Following PRISMA 2020 guidelines, we searched major databases for studies published between 2010 and 2025. Case-control studies and baseline data from trials reporting group means and standard deviations were eligible. Standardised mean differences (Hedges' g) were pooled using random-effects models. Prespecified moderators included age group, medication status and assay or biological matrix.

Across fifteen case-control studies, ADHD was associated with a consistent shift towards oxidative imbalance. Oxidative damage was higher in ADHD for MDA (g = 0.32, 95% CI 0.18-0.46), 8-OHdG (g = 0.27, 0.10-0.44), TOS (g = 0.35, 0.20-0.50) and OSI (g = 0.31, 0.16-0.46). Antioxidant capacity was reduced for TAS (sign-inverted g = 0.25, 0.08-0.42) and SOD (sign-inverted g = 0.22, 0.05-0.39), whereas GPx and CAT showed no consistent differences. Heterogeneity was low to moderate, with no evidence of publication bias. Effects were larger in drug-naïve paediatric samples than in adults or treated cohorts.

ADHD is associated with a small-to-moderate redox imbalance, most pronounced in untreated paediatric populations. These findings support oxidative-antioxidant dysregulation as a biologically meaningful dimension of ADHD and provide a framework for understanding heterogeneity in psychopharmacological response.